The long-range goals of this research program are to identify the mechanisms by which human bone cells age and to clarify the complex relationships between bone cell aging and involutional osteoporosis in humans. The objective of the research proposed is to develop the methodology for studying human bone cell aging at the cellular and subcellular levels in isolated cultured human bone cells in vitro. Human bone cells will be isolated from human bone biopsies obtained systematically at surgery and will be cultured in vitro to monolayer confluence. The morphologic and biochemical responses of these cells to hormonal stimulation will be studied utilizing several parameters, including cAMP generation, collagen synthesis, and alkaline and acid phosphatase activities. Relationship of these functions to in vivo and in vitro aging will be studied. Influence of various hormones on these functions will be investigated. Reversibility of this function as related to aging will be explored by various environmental and hormonal manipulations of the cultured cells. It is hoped that the methodology developed in this project and the information gained on human bone cell aging will suggest methods for reversing or retarding bone cell aging and studying mechanisms of human bone cell aging at the cellular and subcellular levels, in vitro.